Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: Its prevalence and clinical significance

Junji Hiraga, Akihiro Tomita, Takumi Sugimoto, Kazuyuki Shimada, Masafumi Ito, Shigeo Nakamura, Hitoshi Kiyoi, Tomohiro Kinoshita, Tomoki Naoe

研究成果: Article

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Although rituximab is a key molecular targeting drug for CD20-positive B-cell lymphomas, resistance to rituximab has recently been recognized as a considerable problem. Here, we report that a CD20-negative phenotypic change after chemotherapies with rituximab occurs in a certain number of CD20-positive B-cell lymphoma patients. For 5 years, 124 patients with B-cell malignancies were treated with rituximab-containing chemotherapies in Nagoya University Hospital. Relapse or progression was confirmed in 36 patients (29.0%), and a rebiopsy was performed in 19 patients. Of those 19, 5 (26.3%; diffuse large B-cell lymphoma [DLBCL], 3 cases; DLBCL transformed from follicular lymphoma, 2 cases) indicated CD20 protein-negative transformation. Despite salvage chemotherapies without rituximab, all 5 patients died within 1 year of the CD20-negative transformation. Quantitative reverse-transcription-polymerase chain reaction (RT-PCR) showed that CD20 mRNA expression was significantly lower in CD20-negative cells than in CD20-positive cells obtained from the same patient. Interestingly, when CD20-negative cells were treated with 5-aza-2′-deoxycytidine in vitro, the expression of CD20 mRNA was stimulated within 3 days, resulting in the restoration of both cell surface expression of the CD20 protein and rituximab sensitivity. These findings suggest that some epigenetic mechanisms may be partly related to the downregulation of CD20 expression after rituximab treatment.

元の言語English
ページ(範囲)4885-4893
ページ数9
ジャーナルBlood
113
発行部数20
DOI
出版物ステータスPublished - 19-11-2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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